PHSL 3051 Exam 2

Describe arterial pressure changes during the cardiac cycle and how the vascular principle of elastic recoil (also called elastance) permits the vessels (particularly the aorta) to maintain a diastolic pressure.

Arterial properties: - Elastic recoil and Compliance. - Compliance change in volume/pressure. Elastic recoil: ability of a vessel to return back to its original shape after being stretched. - keeps the blood flowing through ventricular relaxation. - Converts an on/off pump to a pulsate flow. During contraction: (compliance) - Aorta and arteries expand and store pressure in elastic walls During relaxation: (Elastic Recoil) - Of arteries sends blood forward into the rest of the circulatory system. - Goes from highest pressure aorta, arteries, arterioles, capillaries, venules, veins, venae cavae

Describe the relationship between blood velocity and total cross-sectional area. Why is blood flow the slowest in the capillaries of any location in the vasculature?

Blood flow: - is the slowest in the capillaries because it has the largest surface area of the vessels, so therefore the slowest flow. Blood velocity: - is how fast moves through the vessel. - The smaller the tube the faster it is, the larger the tube the slower flow. *Veins wouldn't be able to keep up if blood flow was fast. *Slow velocity allows diffusion to go to equilibrium.

Describe function of intercalated discs. Specifically, discuss how gap junctions electrically connect cardiac myocytes and desmosomes physically connect cardiac myocytes. Discuss why this facilitates the myocardium working as a pump (functional syncytium = many cells working as one unit).

Desmosomes: - allow force to be transferred and gap junctions provide electrical connection (permit local current flow). - Allows coordinated contraction

Compare and contrast AV node cells and Purkinje fibers. What are the properties that help the AV node bring about AV delay? What are the properties of the Purkinje fibers that help them spread ventricular depolarization quickly and extensively?

- AV node delay is accomplished by slower conduction signals through nodal cells (small cells with high resistance, fewer gap junctions) - Purkinje fibers spread depolarization rapidly because they are large branching cells with fast conduction signals (many gap junctions)

Draw the structure of the neuromuscular junction including important proteins that are found on the pre and post-synaptic membranes (label these proteins and other structural features)

- Axon terminal of somatic motor neuron releases vesicles onto a motor end plate - Motor end plate has Na+ ligand gated channels

Explain the scientific basis for ECG measurement. In your answer, address the ability of the body to conduct electricity and the placement of the recording electrodes. Students are not held responsible for knowing the lead configurations of all 12 leads but rather understanding how any given lead (two recording electrodes and a ground electrode) is used to detect the ECG.

- Body tissues are based on saline solutions which conduct electricity (depolarization) well. Recording electrodes sense potential difference. - Einthoven's triangle: both arms and the leg. - Leg acts as ground lead. - Reduces interference and dissipates electrical charge.

Name three (3) roles of ATP in skeletal muscle contraction and relaxation.

1. Hydrolysis of ATP by Ca2+ ATPase in SR provides energy for active transport of Ca2+ into SR, lowering Ca2+ cystolic, allowing relaxation 2. Hydrolysis provides energy for cross bridge movement 3. ATP binding to myosin breaks actin-myosin link, allowing next cycle to begin

Explain the role of lymphatic vessels in the maintenance of the interstitial fluid compartment.

Lymphatic vessels: - maintain a balance of fluid and proteins in the interstitial fluid compartment. - Return excess fluid and proteins out of the capillaries to the circulatory system.

Apply the concept of Starling's forces to edema. In other words, how do changes in Starling's forces result in edema (swelling)

2 Main Causes of Edema: 1. Inadequate drainage of lymph 2. Starling forces (Filtration is greater than absorption): - Increase in hydrostatic pressure (ex. Hypertension, venous pressure) - Decrease in plasma protein concentration (liver disease, starvation) - Increase in interstitial proteins (out of the blood, ex. Inflammation)

List the factors that determine the tension developed in a whole muscle and explain how this is controlled.

Number of fibers per motor unit: for fibers of equal size, force proportional to # of fibers in unit Number of active motor units: two are greater than one - Controlled by recruitment through nervous system.

Describe the relationship between blood flow, mean arterial pressure and vascular resistance (Ohm's Law). Describe how changing vessel length, vessel radius and blood viscosity changes the vascular resistance (Poiseulle's Law). These formulae will be provided on the exam. Students should know how to use the formulae to solve pressure and flow problems

Ohm's law: - Current flow (I) is directly proportional to the electrical potential difference (in volts, V) between two points and inversely proportional to the resistance (R) of a system to current flow. - Equation: I = V X 1/R or I = V/R Help with more clarity Poiseulle's Law: - Resistance is proportional to length of the tube, viscosity of blood, and inversely proportional to radius to the fourth power Resistance is influenced by three components: 1. Radius of the tube (r) 2. Length of the tube (L) 3. Viscosity (thickness) of the fluid (n). Equation: R ~ Ln/r^4 This expression says that the resistance to fluid flow offered by a tube increases as the length of the tube increases, resistance increases as the viscosity of the fluid increases, but resistance decreases as the tube's radius increases. - Blood flows down pressure gradient, directly proportional to pressure gradient (mean arterial resistance), inversely proportional to vascular resistance. · If blood vessels dilate, leads to decreased resistance and blood pressure decrease. · If blood vessels contract, leads to increased resistance and blood pressure increases. Increase in volume increases blood pressure.

List the energy sources for muscle contraction and rank the sources with respect to their relative speed and capacity to supply ATP for contraction.

Phosphorylation of ADP by creatine phosphate: · Creatine phosphate (CP): is a "storehouse" of high energy phosphate · In muscle · Rapid amount of ATP generated · limited by initial creatine phosphate in cell, usually lasts only a few seconds Oxidative phosphorylation of ADP: · In mitochondria · Requires O2, for moderate activity (multi-enzyme pathway, initially glycogen provides fuel then blood glucose and fatty acids do) · major ATP provider Phosphorylation of ADP by glycolysis: · In cytoplasm · Slow, for higher intensity activity (glucose from blood or glycogen) · Two ATP/glucose but can produce quite rapidly with enough enzymes/substrates

Define a motor unit and describe the order of recruitment of motor units during skeletal muscle contractions producing low, moderate and high amounts of tension.

Motor unit: somatic motor neuron and the muscle fibers surrounding it innervates · Only one motorneuron innervates a single skeletal muscle, but each motorneuron may innervate multiple fibers. Low tension: · Weak stimulus activates lowest thresholds, usually slow-oxidative which are resistant to fatigue. Moderate tension: · As stimulus increases, fatigue-resistant fast-twitch oxidative-glycolytic fibers are recruited. High tension: · As the stimulus increases even more, motor units with fast-glycolytic fibers are recruited.

Discs, Bands, Zone, and Line

Z Discs: - Narrow, plate-shaped regions of dense material that separate one sarcomere from the next. A Band: - The dark, middle part of the sarcomere that extends the entire length of the thick filaments and also includes those parts of the thin filaments that overlap with the thick filaments. I Band: - The lighter, less dense area of the sarcomere that contains the rest of the thin filaments but no thick filaments. A Z disc passes through the center of each I band. H Zone: - A narrow region in the center of each A band that contains thick filaments but no thin filaments. M Line: - A region in the center of the H zone that contains proteins that hold the thick filaments together at the center of the sarcomere.

Describe the parts (receptor, sensory neuron, integrator, motor neuron, effector=target) of the baroreceptor reflex arc.

Receptor: - baroreceptor is the aorta and carotid arteries detect changes in BP stimulus. Sensory neurons: - Visceral afferent neurons to the control center. - Send frequency of action potentials based on the amount of depolarization in the baroreceptor. Cardiovascular integration center: - decides what to do with the stimulus about the blood pressure Motor neurons: - Sympathetic release NE onto alpha receptors in the arteriolar smooth muscle and onto beta receptors in the ventricular myocardium and onto the SA node. - Sympathetic onto just SA node through ACh onto muscarinic receptors. Effectors: - Smooth muscle of the arterioles: constriction, dilation. - Ventricular myocardium: force of contraction. - SA node: heart rate

Diagram the chemical and mechanical steps in the cross-bridge cycle, and explain how the crossbridge cycle results in shortening of the muscle.

Shortening of muscle process via crossbridge: 1. Energy: · Myosin head includes an ATP-binding site that functions as an ATPase—an enzyme that hydrolyzes ATP into ADP (adenosine diphosphate) and a phosphate group 2. Binding: · energized myosin head attaches to the myosin-binding site on actin and releases the previously hydrolyzed phosphate group. · Crossbridge: myosin head that attaches to actin during the contraction cycle 3. Power stroke: · myosin head pivots (90° to 45°) it pulls the thin filament past the thick filament toward the center of the sarcomere, generating tension (force) in the process · Energy required for power stroke from energy stored in myosin head from hydrolysis of ATP 4. Detachment: · Crossbridge remains attached to actin until it binds to another ATP molecule · As ATP binds to ATP-binding site on myosin head, the head detaches from actin · cross bridge detaches at end of power stroke and returns to original conformation. · Cycle Repeats

Describe how smooth muscle activation and relaxation differ from the activation and relaxation of skeletal muscle

Smooth: - Thin filament lack troponin, but have tropomyosin - Tropomyosin does not cover myosin-binding sites on actin - Myosin molecules can bind to actin only after phosphate groups are added to light chains in myosin heads - activation and relaxation slower than skeletal Skeletal: - Ca2+ binds to troponin causing tropomyosin to move away from myosin-binding sites on actin - Myosin-binding sites are exposed, myosin attaches to actin *Results in muscle contraction

List the regions of the brain involved in middle level of motor control and describe the main function that these structures serve.

Spinal Cord: spinal reflexes, locomotor pattern generators Brain Stem: Posture, hand and eye movements Parts of Brain Stem: · Vestibular Nuclei: help control posture and balance · Reticular Formation: regulates posture and muscle tone during movements · Superior Colliculus: assists with movements of the head, trunk and saccadic eye movements · Red Nucleus: controls voluntary movements of the upper limbs Cerebellum: monitors output signals from motor areas and adjusts movements Thalamus: contains relay nuclei that modulate and pass messages to cerebral cortex Basal Nuclei: initiation of movement and the suppression of unwanted movements. · Disorders: · Parkinson's Disease · Huntington's Disease · Tourette's syndrome

Explain how each of the Starling's forces (capillary hydrostatic, capillary protein osmotic, interstitial hydrostatic, interstitial protein osmotic) contributes to capillary filtration and flow into the lymphatic vessels.

Starling hypothesis: - Fluid movement is due to filtration across the wall of a capillary is dependent on the balance between the hydrostatic pressure and the oncotic pressure across the capillary Capillary hydrostatic: - movement of fluid OUT of the cell Capillary protein osmotic: - movement of fluid INTO the cell Interstitial protein osmotic: - movement of fluid OUT of the cell Interstitial hydrostatic: - movement of fluid OUT of the cell Filtration: fluid movement out of the capillaries, caused by hydrostatic pressure (net filtration in arteries) Absorption: fluid movement into the capillaries, caused by colloid (protein) osmotic pressure (net absorption in veins) Net filtration= [(capillary hydrostatic pressure + interstitial oncotic pressure) - (interstitial hydrostatic pressure + capillary oncotic pressure)]

Distinguish between a single twitch and a tetanic contraction in skeletal muscle and explain why twitch response is smaller in amplitude than a tetanic contraction.

Twitch: - one contraction of a group of muscle fibers within a muscle in response to a single action potential Tetanic Contraction: - maximal contraction - maintained contraction because repetitive stimulation · Unfused tetanus (incomplete): skeletal muscle fiber stimulated at higher rate, can relax only slightly between stimuli · Fused tetanus (complete): skeletal muscle fiber stimulated at even higher rate, does not relax at all *Twitch is smaller in amp because summation occurs in tetanus; tetanus has persistent elevation of cystolic Ca so more binding sites available and more bridges bind to actin

Calculate the CO from the product of HR and SV. Note that SV = EDV-ESV. Students should know this formula. Students should know that an average CO is 5 L/min

This is a way to assess the effectiveness of the heart as a pump · SV = EDV-ESV *volume of blood before contraction - volume of blood after contraction = SV · Average CO is 5 L/min. SV: the amount of blood pumped by one ventricle during a contraction

Explain how a baroreceptor works i.e. what makes it depolarize, where it sends information to, what are the consequences of that information.

- Change in BP (increase or decrease) is sensed by the baroreceptor in the carotid arteries and aorta which leads to an increased or decreased amount of depolarization of the baroreceptor - The magnitude of depolarization is conveyed to the brain stem through the frequency of action potentials in VISCERAL AFFERENT neurons. - The control center integrates the information with a set point. If BP is too high both the parasympathetic and sympathetic motor systems are activated - The motor pathways synapse onto effectors EFFECTORS: Arteriolar smooth muscle: - Sympatheic system has less NE released. - Binds to alpha receptor on smooth muscle. - Less NE causes it to dilate which leads to a decrease in peripheral resistance Ventricular Myocardium: - Sympathetic motor system has less NE released. - Binds to Beta 1 receptors. - Less NE decreases the force of contraction. - Leading to a decreased cardiac output SA Node: - Sympathetic motor system has less NE released. - Binds to Beta 1 receptors - Less NE decreases the heart rate. - Leading to a decreased cardiac output. - Parasympathetic motor system has more ACh released onto muscarinic receptors. - This leads to a decrease in heart rate. THIS SYSTEM WORKS TO EITHER INCREASE OR DECREASE BLOOD PRESSURE BASED ON THE STIMULUS. IT IS A NEGATIVE FEEDBACK LOOP

Compare and contrast the electrical activity of skeletal and cardiac muscle cells. Consider the duration and ionic basis of the skeletal and cardiac action potentials, and the functional consequences of their differences.

- Contraction of smooth muscles controlled by autonomic nervous system and contraction can be initiated by electrical or chemical signals. Actin is plentiful, lacks troponin - Skeletal muscle is controlled by somatic motor division and always begins with an action potential

Contrast the duration of a muscle action potential with the duration of a muscle contraction, and explain the significance of this difference.

- Increased Ca2+ concentration continues to activate contractile apparatus long after AP ceased - Ca2+ ATPase that pumps Ca2+ into SR takes a while, contraction continues for some time after AP

Discuss the deflections (as electricity is flowing through the heart) and isoelectric events (when the heart is totally depolarized or repolarized) of the ECG. Specifically discuss what electrical event is occurring during the P wave, the QRS complex and the T wave.

- P wave: atrial depolarization - P-R segment: conduction through AV node and AV bundle - QRS complex: ventricular depolarization - T-wave: ventricular repolarization

Define preload making sure to include sarcomere length in your answer. Discuss how venous return regulates cardiac output (Frank-Starling law of the heart).

- Preload is the degree of myocardial stretch before contraction. The cellular basis for preload is sarcomere length. Stretch adjusts the sarcomeres to an optimal length, *The more you fill, the more you eject, the more forceful the ejection. Increase in venous return stretches the heart muscle and results in larger stroke volume. Frank-Starling law of the heart: - equalizes the output of the right and left ventricles and keeps the same volume of blood flowing to both the systemic and pulmonary circulations. - If the left side of the heart pumps a little more blood than the right side, the volume of blood returning to the right ventricle (venous return) increases. - The increased EDV causes the right ventricle to contract more forcefully on the next beat, bringing the two sides back into balance.

Discuss how neural (baroreceptors) and hormonal (RAAS) mechanisms work together to maintain BP. Explain the functions of aldosterone and angiotensin II.

- RAAS mechanism works to raise BP/hydrostatic pressure - Low BP causes renin release from kidney Angiotensin II: - Vasoconstrictor - Increases vascular resistance and blood pressure Aldosterone: - Kidney hormone - Increases plasma volume and blood pressure

Describe Ca2+ accumulation in the sarcoplasmic reticulum mediated by Ca2+-ATPase. Explain the role that these (Ca2+-ATPase pump proteins) transporters play in muscle function.

- Sarcoplasmic Calcium ATPase pumps calcium back into sarcoplasmic reticulum - Decrease in free cytosolic Ca2+ causes Ca2+ to unbind from troponin - As crossbridges release, the muscle fiber relaxes with the help of elastic fibers in the sarcomere in the connective tissue of the muscle

Draw and label a diagram that shows skeletal muscle at all anatomical levels. Illustrate the structural characteristics of whole muscle (intact muscles attached to the skeleton), single muscle cells, myofibrils and sarcomeres. At the sarcomere level your drawing should identify the molecular components that are the basis of its striated appearance. Include two different stages of myofilament overlap.

- Skeletal muscles are made up of muscle cells (muscle fibers) - Each skeletal muscle fiber is sheathed in CT, with groups of adjacent muscle fibers bundled together into units called fascicles. - The entire muscle is enclosed in a connective tissue sheath that is continuous with the CT around the muscle fibers and fascicles and with the tendons holding the muscle to underlying bones - Myofibrils are highly organized bundles of contractile and elastic proteins that carry out the work of contraction. Whole Muscle: - composed of connective tissue, muscle fascicles, blood vessels, and nerves Single Muscle: - One muscle fiber contains a thousand or more myofibrils that occupy most of the intracellular volume, leaving little space for cytosol and organelles Myofibrils: - Contains several proteins - Contractile proteins: myosin and actin - Regulatory proteins: tropomyosin and troponin - Giant accessory proteins: titin and nebulin Sarcomeres: - At its resting length, you see that within each sarcomere, the ends of the thick and thin filaments overlap slightly. - A sarcomere has a large I band (thin filaments only) and an A band whose length is the length of the thick filament Myofilament overlap (2 stages): - When the muscle contracts, the thick and thin filaments slide past each other. - The Z disks move closer, the I band and H zone (regions where actin and myosin do not overlap in resting muscle) almost disappear. - The length of the A band remains constant.

What sets the basic heart rate rhythm? Predict the outcome if all nerves to the SA node were severed.

- The SA node of the heart sets the basic heart rate rhythm. - If all nerves to the SA node were severed it would still continue to beat because the heart does not require any outside neural stimulus to contract.

List the factors that determine the tension developed in a whole muscle and explain how each contributes to the amount of tension generated.

1) the number of muscle fibers stimulated 2) the relative size of the fibers 3) frequency of stimulation 4) the degree of muscle strength

List the factors that determine the tension developed by single muscle fibers and explain the molecular basis for each factor.

1. AP Frequency- multiple AP can lead to summation of successive muscle contractions because Ca remains; stimuli closer together = more force 2. Fiber length: there is an optimum length at which a muscle develops max tension due to optimum myosin and actin overlap 3. Fiber diameter: greater number of thin and thick acting in parallel to produce force Muscle fibers: Thick diameter: · more myofibrils · Generate more tension · Exert more force than thinner diameter Thin diameter: · Less myofibrils · Less tension Motor Unit Size: Small motor Units: · Muscles that control precise movement · Involve small amounts of force EX: eye Large motor units: · Large-scale and powerful movements EX: calf Motor unit recruitment: Process of increasing the number of active motor units 4. Fatigue: repeated stimulation decrease tension

List the steps in excitation-contraction coupling in skeletal muscle, and describe the roles of the sarcolemma, transverse tubules, sarcoplasmic reticulum and the thin and thick filaments. Be certain to include the roles of modulatory proteins such as troponin and tropomyosin and of calcium ions.

1. Nerve AP in somatic motor neuron triggers release of ACh 2. ACh binds to receptors in motor end plate, triggering an end plate potential which generates a muscle action potential 3. Acetylcholinesterase destroys ACh so another muscle AP doesn't arise unless more ACh is released from somatic motor neuron 4. Muscle AP travels along transverse tubule triggers change in dihydropyridine receptor (DHR, L-type VG Ca2+ channel) that causes Ca2+ release channels (ryanodine channel) to open allowing release of Ca2+ ions into sarcoplasm 5. Ca2+ binds to troponin on the actin filament, exposing myosin-binding sites on actin 6. Increase Ca2+ levels Contraction: myosin heads bind to actin, undergo power strokes and release - actin filament are pulled toward center of sarcomere 7. Ca2+ release channels close and Ca2+ ATPase pumps use ATP to restore low level of Ca2+ in sarcoplasm 8. Tropomyosin slides back into position where it blocks the myosin-binding sites on actin 9. Muscle relaxes Sarcolemma: initiates action potential T-tubules: allow AP to move rapidly from the cell surface into the interior of the fiber Sarcoplasmic reticulum: stores Ca2+ Troponin: Controls the "off-on" positioning of tropomyosin Tropomyosin: wraps around actin filaments and partially covers actin's myosin-binding sites during "off" position; uncover during "on" position

Describe the flow of depolarization through the conducting pathway, particularly noting how the depolarization starts in the SA node, is slowed at the AV node and then is rapidly transmitted throughout the ventricles by the Purkinje fibers.

1. SA node sets the pace of the heart (depolarizes) 2. Electrical activity goes rapidly to AV node via intermodal pathways 3. Depolarization spreads more slowly across atria. Conduction slows through AV node 4. Depolarization moves rapidly through ventricular conducting system to the apex of the heart (through purkinje fibers)

Describe the three layers of vessels (connective tissue for strength and elastance), smooth muscle for regulating of the radius size and endothelium for a smooth lining) and apply characteristics of the layers to the function of a given vessel. For example the aorta has mostly connective tissue, helping it to stretch and spring back during the cardiac cycle. This connective tissue also helps the aorta withstand the high pressure, high velocity blood flow exiting the left ventricle. Repeat this thought process for arterioles, capillaries and veins

3 layers of vessels: 1. Connective tissue: strength and elasticity - Vein: smooth, elastic, and fibrous tissue, low pressure, (hold more than half of the blood of the circulatory system because there are more and have larger diameter), highest capacitance - Venule: fibrous tissue 2. Smooth muscle: regulating the radius size - Artery: smooth muscle, elastic tissue, and fibrous tissue, divergent blood flow (high pressure and high velocity) - Arteriole: smooth muscle, high resistance, thick wall, selectively constrict and dilate (innervated by the sympathetic nervous system) 3. Endothelium: smooth lining - Capillary: endothelium, exchange between blood and cells takes place at the capillaries, slowflow and thin wall Size: Vein > Artery > Arteriole > Venule > Capillary Pressure: Aorta > Arteries > Arteriole > Capillary > Venule > Vein > Venae cavae Arterial Properties Compliance: o Change in volume/change in pressure o Compliance decreases with age o Veins more compliant than arteries Elastance: o Ability of vessel to return to original shape after stretch o Elastic recoil of the arteries keeps blood flowing during diastole o Converts an on/off pump to a continuous, pulsatile blood flow

Define afterload and discuss situations in which a high afterload could decrease the stroke volume. The opening and closing of the semilunar valves should factor into your answer. Specifically students should understand that the left ventricle is more muscular than the right ventricle because the left ventricle pumps against 5 times the afterload as compared to the right ventricle.

Afterload: pressure that must be overcome before a semilunar valve can open - Ejection of blood from the heart begins when pressure in the right ventricle exceeds the pressure in the pulmonary trunk (about 20 mmHg) and when the pressure in the left ventricle exceeds the pressure in the aorta (about 80 mmHg). When Afterload occurs: - The higher pressure in the ventricles causes blood to push the semilunar valves open. - An increase in afterload causes stroke volume to decrease so that more blood remains in the ventricles at the end of systole. - Conditions that can increase afterload include hypertension (elevated blood pressure).

Describe role of arterioles in blood distribution since we don't have enough blood to send to every body part all the time. In other words, how do the arterioles make sure that blood goes where it is needed? Be able to give examples of local factors that regulate blood flow.

Arterioles: - create a high-resistance outlet for arterial blood flow - Direct distribution of blood flow to individual tissues by selectively constricting and dilating, so they are known as a site of variable resistance. - This is regulated by tissue oxygen concentrations and by the autonomic nervous system and hormones. Systemic Nervous System: - releases norepinephrine on alpha receptors to constrict the blood vessels away from the GI tract and towards other areas. Hormones also control blood distribution: - epinephrine is released from the adrenal medulla on to Beta 2 receptors that dilate blood vessels going to skeletal muscle, the heart, and liver. Myogenic autoregulation: - the ability of smooth muscles in blood vessels to regulate own contraction. In brain and kidney. Opens voltage gated Ca2+ channels

List the potential sources of calcium that contribute to smooth muscle activation.

Ca2+ flows into smooth muscle sarcoplasm from two sources: 1. Most comes from extracellular fluid 2. Rest from the sarcoplasmic reticulum (SR). - To enter the sarcoplasm, Ca2+ ions move across the sarcolemma of the smooth muscle fiber or the membrane of the SR by passing through ion channels. - Because SR is present in small amounts in smooth muscle, it provides only a small portion of the Ca2+ needed for contraction. Contraction (increase of Ca2+ in smooth muscle): 1. Ca2+ binds to calmodulin, a regulatory protein in the sarcoplasm that is similar in structure to troponin. 2. The Ca2+-calmodulin complex activates an enzyme called myosin light chain kinase (MLCK), which is also present in the sarcoplasm. 3. Activated MLCK in turn phosphorylates (adds a phosphate group to) light chains in the myosin heads. 4. The phosphorylated myosin heads bind to actin, and muscle contraction begins. Relaxation of smooth muscle: 1. Ca2+ is removed from the sarcoplasm by Ca2+ ATPase pumps in the SR membrane and by Na+-Ca2+ exchangers in the sarcolemma. 2. Ca2+ concentration decreases, Ca2+ dissociates from calmodulin, and myosin light chain kinase becomes inactive. 3. Dephosphorylation of myosin heads (removing the phosphate group from light chains in the myosin heads) occurs via enzyme myosin phosphatase. 4. Once the phosphate groups are removed, the myosin heads are unable to bind to actin, and the smooth muscle fiber relaxes. MLCK: - Myosin light chain kinase works rather slowly. - The ATPase activity of myosin heads in smooth muscle is much slower than in striated muscle *Due to the removal of Ca2+ from sarcoplasm is slower in smooth muscle than skeletal muscle

Describe how the structure of a capillary enables capillary exchange

Capillaries: - Very thin walled. The thickness of the capillaries depends on the metabolic needs of the tissue. - They are slow flowing to allow for exchange. - Continous capillaries have leaky channels and blood cannot pass through them.

Discuss the mechanical and electrical events of the cardiac cycle during diastole and systole from the Cardiac Cycle Diagram. Not only should student follow each graph, sounds, ECG, volume curve, pressure curve, etc. they should also be able to move up and down the diagram from curve to curve. For example, after the P wave, one should see an increase in atrial pressure as a result of atrial contraction. This diagram will be provided on the exam.

Cardiac cycle begins during period when atria and ventricles are diastole. Passive Ventricular Filling: 1. Atrial pressure is higher than ventricular pressure --> atria are filling with blood returning to the heart by veins. *Results in, pressure difference, the atrioventricular (AV) valves open, and blood flows from the atria into the ventricles. *No muscle contractions 2. Semilunar values are closed at this time --> aortic pressure is higher than left ventricular pressure and pulmonary trunk pressure is higher than right ventricular pressure. 3. At the end of atrial diastole, an action potential arises in the SA node and then propagates throughout the atria, causing the atria to depolarize. - Atrial depolarization is indicated by the P wave on the ECG Atrial Contraction: 4. Atrial depolarization causes atrial systole. - While the atria are in systole, the ventricles remain in diastole. As the atria contract, atrial pressure increases and more blood is forced through the open AV valves into the ventricles. 5. End of atrial systole is also the end of ventricular diastole (relaxation). - Thus, each ventricle contains about 130 mL at the end of its relaxation period (diastole). - This blood volume is called the end-diastolic volume (EDV) 6. Toward the end of atria systole, the QRS complex appears on the ECG, marking the onset of ventricular depolarization Isovolumetric Ventricular Contraction: 7. Ventricular depolarization causes ventricular systole. - While the ventricles are in systole, the atria are in diastole. - As ventricular systole begins, pressure rises inside the ventricles and pushes blood up against the AV valves, forcing them shut - For a brief moment, both the AV and SL valves are closed. - Cardiac muscles are contracting and exerting force but not shortening (muscle contraction is isometric [same length]) - all four valves are closed, ventricular volume remains the same (isovolumic). Ventricular Ejection: 8. Left ventricular pressure surpasses aortic pressure at about 80 mmHg and right ventricular pressure rises above pulmonary trunk pressure (about 20 mmHg), both SL valves open - blood is pumped out of the heart 9. Left ventricle ejects about 70 mL of blood into the aorta, and the right ventricle ejects the same volume of blood into the pulmonary trunk. - The volume remaining in each ventricle at the end of systole, about 60 mL, is the end-systolic volume (ESV) - Stroke volume, the volume ejected per beat from each ventricle - Changes in stroke volume alter the ejection fraction 10. Near the end of ventricular systole, the T wave appears on the ECG, marking the onset of ventricular repolarization Isovolumetric Ventricular Relaxation: 11. Ventricular repolarization causes ventricular diastole. - As the ventricles relax, pressure within the chambers falls, and blood in the aorta and pulmonary trunk begins to flow backward toward the regions of lower pressure in the ventricles. - Backflowing blood catches in the valve cusps and closes the SL valves 12. Rebound of blood off the closed cusps of the aortic valve produces the dicrotic wave on the aortic pressure curve - After the SL valves close, there is a brief interval when ventricular blood volume does not change because all four valves are closed. 13. As the ventricles continue to relax, the pressure falls quickly. - When ventricular pressure drops below atrial pressure, the AV valves open and another cardiac cycle repeats as passive ventricular filling begins.

Discuss the factors that regulate the cardiac output (CO): heart rate, preload, contractility and afterload.

Cardiac output (CO) is influenced by heart rate: - Determined by the rate of depolarization in autorythmic cells. *HR decreases due to parasympathetic innervation (ACh). *HR increases due to sympathetic innervation (NE) Stroke Volume: - determined by the contraction of the ventricular myocardium which is influenced by contractility and end diastolic volume Symphathetic innervation and epinephrine increases contractility: - EDV varies with venous return which is aided by skeletal muscle pump and respiratory pump. - Sympathetic innervation and epinephrine increases venous constriction which increases venous return. Factors affecting stroke volume: - Contractility: intrinsic ability of a cardiac muscle fiber to contract at any given fiber length and is a function of Ca2+ interaction with contractile filaments - Preload: degree of myocardial stretch before contraction (length of muscle fiber) - Afterload: total amount of EDV load and arterial resistance during ventricular contraction

Define contractility and discuss the importance of intracellular calcium to contractility.

Contractility: the intrinsic ability of the myocardium to contract. Inotropic effect: Any chemical agent that affects contractility Positive intropic effect: Epinephrine, norepinephrine and digitalis are all positive agents - they increase contractility by increasing the amount of intracellular calcium ions. - This increases allows for a more forceful contraction. - The Ca-ATPase also removes calcium from the cytosol faster, so there is a shortened Ca-troponin binding time leading to a shorter duration of contractions

Give an overview of the function of the organelles (T-tubules, sarcoplasmic reticulum, contractile apparatus) and proteins (voltage-gated Ca2+ channels and SR calcium release channels) that are responsible for excitation-contraction coupling in cardiac muscle (i.e. calcium induced calcium release). Remember that you have encountered some of these proteins in neurons and skeletal muscle cells. Build on your previous knowledge.

Excitation-contraction of Cardiac Muscles: 1. Action potential travels along the sarcolemma and into the T tubules, where it causes the L-type voltage-gated Ca2+ channels to open. 2. The entering Ca2+ functions as trigger Ca2+ that binds to and opens the Ca2+ release channels in the SR membrane. *Results in additional Ca2+ enters the sarcoplasm from the SR. 3. The process by which extracellular Ca2+ triggers the release of additional Ca2+ from the SR is known as Ca2+ -induced Ca2+ release (CICR) - L-type voltage-gated channels (dihydropyridine receptors) in the T-tubule membrane is close to, and has an effect on, only one Ca2+ release channel in the SR membrane

Construct a table of structural, enzymatic, and functional features of fast-glycolytic, fast oxidative, and slow-oxidative fiber types from skeletal muscle.

Fast-oxidative: - (hybrid) intermediate size because needs O2, can't get too big Structural: Numerous mitochondria/blood vessels/myoglobin Enzymatic: fast myosin-ATPase Function: Fast running, intermediate distances, generates mod tension Fast-glycolytic: - (glycolytic metabolism) Structural: Larger diameter, few mitochondria/myoglobin, many fibers per unit Enzymatic: Fast myosin ATPase, high glycolytic enzymes Function: Large tension over short time because large diameter and fast myosin ATPase, fatigue most likely Slow-oxidative: - (slower crossbridge cycle = lower max velocity of shortening) Structural: Numerous mito/blood vessels/myoglobin, small diameter, few fibers per unit Enzymatic: slow myosin ATPase Function: Maintain activity without fatigue, posture, generate least tension because small diameter and slow myosin

Describe the function of higher centers in motor control.

Function: - Forms complex plans according to individual's intention and communicates with the middle level via "command neurons." Structures: - areas involved with memory and emotion, supplementary motor area, and association cortex. All receive and correlate input from other brain structures.

Describe the role of the gamma efferent system and explain the significance of alpha-gamma co-activation.

Gamma motor neurons: - stimulate intrafusal fibers to contract and "reset" their sensory signals so the system · In normal muscle keeps the muscle spindles active even when muscle length is stretched of shortened Alpha-gamma coactivation: - maintains spindle function when muscle contracts. · Excitation of gamma motor neurons and alpha motor neurons at the same time 1. Alpha and gamma motor neuron fire 2. Muscle and intrafussal fibers both contract 3. Stretch on centers of intrafussal fibers unchanged. Firing rate of afferent neuron remains constant. · Alpha motor neurons innervate extrafusal fibers, gamma motor neurons innervate intrafusal fibers

Discuss the dual innervation of the heart and the regulation of HR and SV by ANS. Both the parasympathetic and sympathetic nervous systems innervate the SA node but these two systems have opposite effects on the heart rate. Identify which neurotransmitters are released by each branch. Discuss the mechanism of this modulation of the heart rate by neurotransmitters (i.e. which channels are opened).

HR: - determined by rate of depolarization in auto rhythmic cells and decreases due to parasympathetic innervation and increases due to sympathetic innervation and epinephrine SV: - determined by force of contraction in ventricular myocardium. - Influenced by contractility and EDV which varies with venous return which is aided by skeletal muscle pump, respiratory pump, and venous constriction Sympathetic: - NE is released through the sympathetic system onto the B1 receptor of auto rhythmic cells. - Speeds up the heart rate. Sympathetic stimulation and epinephrine depolarize the autorythmic cell and speed up the pacemaker potential. - The catelcholmines increase the ion flow through both Ion flow channels and Ca2+ channels. - More rapid cation entry speeds up the rate of pacemaker depolarization, causing the cell to reach threshold faster and increasing the rate of action potentials firing. - Catelcholmines bind and active B1-adrenergic receptors on the autorythmic cell. - These receptors use a cAMP second messenger to alter the transport properties of the ion channels. - When cAMP binds to open Ion flow channels they remain open longer. - Increased permeability to Na+ and Ca+ during pacemaker potential phase speeds up depolarization and heart rate. Parasympathetic: - ACh is released onto the Muscarinic receptor of auto rhythmic cells. - Hyperpolarizes the membrane potential of the autorythmic cell and SLOWS depolarization - ACh activates muscarinic cholinergic receptors that influence Ca2+ and K+ channels in the pacemaker cell. - K+ permeability increases and hyperpolarizes the cell, making a more negative membrane potential. - Ca2+ permeability of pacemaker cell decreases. - Decreased Ca2+ permeability slows the heart rate at which the cell can depolarize.

Discuss intrinsic (local tissue factors) and extrinsic (sympathetic nerves and hormones) regulators of arteriolar smooth muscle tone. Big picture idea is as follows: intrinsic, local factors regulate blood flow whereas extrinsic factors regulate blood pressure.

Intrinsic factors: - Regulate blood flow in the area. - Local factors of blood flow are in response to metabolic needs of tissues. - Increased CO2, H+,K+, NO leads to more blood flow. - Decreased O2 leads to increased blood flow. Extrinsic factors: - are the sympathetic nerves and hormones. - Regulate blood pressure Sympathetic nerves: - Norepinephrine on alpha receptors that constrict the vessels. EX: GI tract: - The adrengic receptor and epinephrine on Beta 2 receptors vasodilates blood vessels to areas such has the heart, liver, and skeletal muscles. Hormone: - Longer term effect. - Angiotensin II is a vasoconstrictor, it INCREASES vascular resistance, Increased BP/hydrostatic pressure. Aldosterone: - works through the kidneys. Increases plasma volume which increases blood pressure/hydrostatic pressure

Compare and contrast isometric and isotonic muscle contractions with respect to the duration of the latent period, the velocity of contraction and the circumstances under which each type of contraction will take place.

Isotonic: - tension remains constant as muscle length decreases or increases - a contraction that creates force and moves a load · Concentric isotonic contraction: tensions generated by the muscle fiber greater than the load placed on the muscle fiber, it will shorten the muscle and pull on another structure (tendon) to produce movement · Eccentric isotonic contraction: When the length of a muscle increases during a contraction · tension exerted by the myosin crossbridges resists movement of a load and slows the lengthening process. · Latent period = Longer (includes time for EC coupling AND extra time to accumulate enough bridges to lift load) · velocity = briefer shortening, velocity decreases with heavier load Isometric: - tension generated is not enough to exceed the load, and the muscle does not change its length (A contraction that creates force without moving load) · load on the muscle is not overcome by the tension generated by the sarcomere shortening · Latent period = shorter

Compare and contrast laminar (smooth and quiet) and turbulent flow (disorganized flow). Discuss how these two kinds of flow are important to determining blood pressure with a blood pressure cuff. Specifically, students should discuss principles of noninvasive measurement of the BP i.e. occlusion of the vessels with the blood pressure cuff and using Korotkoff sounds to determine diastolic and systolic pressure.

Laminar flow (no sound) and turbulent flow (causes Korothoff sound) · Pressure above 120 mmHg, cuff stops arterial blood flow so no sound can be heard through stethoscope. · When cuff is between 80-120 mmHg, Korothoff sounds are created by pulsatile blood flow through the compressed artery. · When cuff is <80 mmHg, blood flow is silent. First Korothoff sound= systole, no more Korothoff sound= diastole - The occlusion of vessels help us to hear the Korotkoff sounds Turbulent flow: - the first sound heard represents the highest pressure in the artery and is recorded as the systolic pressure Laminar flow: - The last sound heard represents the lowest pressure in the artery and is recorded as the diastolic pressure

Explain why in lead II, the QRS and T wave are both in the upward (positive) deflection. As part of this objective, students should consider the refractory periods of the myocytes at the base and the apex of the heart.

Lead 2: - is strongest and largest deflection because it is most parallel to general flow of depolarization in the heart.

Describe the relationship between different degrees of myofilament overlap and the shape of the length-tension relationship

Length-tension relationship: - the forcefulness of muscle contraction (tension) depends on the length of sarcomeres within a muscle fiber before contraction begins. Sarcomeres of muscle fibers stretched to longer length (overstretched): · Barely Overlap: shortens and fewer myosin heads can make contact with thin filament (few crossbridges form) · TENSION DECREASES Sarcomere length shorter than optimum (understretched): · Will Overlap: the thick filaments crumple as they are compressed by the Z discs, resulting in fewer myosin heads making contact with thin filaments (preventing crossbridge formation) · TENSION DECREASES RAPIDLY Skeletal muscle fiber stretch to 170% of optimal length: · No overlap: none of the myosin heads can bind to thin filaments, the muscle fiber cannot contract · TENSION = ZERO

Calculate mean arterial pressure (diastolic + 1/3 (systolic-diastolic)) & describe BP measurement using a blood pressure cuff. Students should know this formula.

Mean arterial pressure: - is proportional to cardiac output x peripheral resistance. · If blood vessels dilate, decreased resistance and increased flow, BP decreases. · If blood vessels constrict, increased resistance and decreased flow, BP increases. - Increase in stroke volume (increase in plasma volume) increases the BP

Use your knowledge of the flow of blood through the heart to explain the operation of the valves and the events of the cardiac cycle. Explain mechanism of valve opening/closing. Explain the importance of pressure gradients for valves to open and close.

Mechanism of valve opening/closing: Opening and closing controlled by pressure gradients generated during cycle Atrioventricular valves: - Between atria and ventricles (prevent flow backward into atria during ventricular contraction) - Tricuspid valve on the right side - Bicuspid valve, or mitral valve, on the left side Semilunar valves - Between ventricles and arteries (prevent blood that has entered arteries from flowing back into ventricles during ventricular relaxation) - Aortic valve - Pulmonary valve Importance of pressure gradients for valves to open and close: - Once pressure in the atrium exceeds pressure in the ventricle, the mitral valve between the atrium and ventricle opens. - When ventricular contraction begins, the mitral valve closes. - Once ventricular pressure exceeds the pressure in the aorta, the aortic valve opens. - When ventricular pressure falls below aortic pressure, the semilunar valve closes and the ventricle again becomes a sealed chamber

Compare and contrast the structure, anatomical location, and function of muscle spindles and Golgi tendon organs.

Muscle Spindles: Anatomical Location: · In every skeletal muscle (except one in jaw) · Scattered among contractile extrafusal muscle fibers (normal contractile) · Anchored parallel to contractile extrafusal muscle fibers Structure: · Have stretch receptors · Small, elongated structures Function: · Respond (send info) to muscle stretch · Send info to spinal cord and brain about muscle length and changes in muscle length · Movement that increases muscle length, stretch the muscle spindles · Causes sensory fibers in muscle spindles to fire rapidly · Creates reflex contraction of muscle to prevent damage from overstretching · Communication: · Extrafusal muscle fiber at resting length · Sensory neuron is tonically active · Spinal cord integrates function · Alpha motor neurons to extrafusal fibers receive tonic input from muscle spindles · Extrafusal fibers maintain a certain level of tension even at rest. Golgi Tendon: Anatomical Location: · In skeletal muscle tendon · Found at the junction of tendons and muscle fibers · Are in series with muscle fibers Structure: · Composed of free (sensory) nerve ending that intertwine between collagen fibers inside a connective tissue capsule Function: · Respond to muscle tension created during isometric contraction · Links muscle to tendon · Relatively insensitive to muscle stretch · Cause relaxation · Opposite to reflex contraction caused by muscle spindles · Muscle contracts: · Tendons act as elastic component · Contraction pulls collagen fibers within Golgi tendon tight, pinching sensory endings of afferent neurons and causing them to fire · Afferent input from activation of Golgi tendon excites the inhibitory interneurons in spinal cord · Most cases, Golgi tendon organ reflexes slows muscle contraction and in other causes they prevent excessive contraction that might injure the muscle Force Feedback: · Neuron from Golgi tendon organ fires · Motor neuron is inhibited · Muscle relaxes · Load is dropped

List in sequence the steps involved in neuromuscular transmission for skeletal muscle and point out the location of each step on a diagram of the neuromuscular junction; name the neurotransmitter and describe three ways the neurotransmitter molecules in the synaptic cleft are removed after the nerve stops sending signals.

Neuromuscular transmission: - at the skeletal muscle, occurs when acetylcholine from the nerve ending is released and binds to the nicotinic acetylcholine receptors on the postjunctional muscle membrane. - Nicotinic acetylcholine receptors on the endplate respond by opening channels for the influx of Na+ ions and subsequent endplate depolarization leads to muscle contraction. - Acetylcholine immediately detaches from the receptor and is hydrolysed by acetylcholinesterase enzyme.

Relate the electrical events represented by the ECG with the mechanical events represented by the pulse tracing.

P-wave: - atrial depolarization (small upward wave) QRS complex: - ventricular depolarization (downward deflection/large upward peak/downward deflection) T-wave: - ventricular re-polarization (dome shaped wave)

Relate principles of negative feedback to blood pressure regulation. Blood pressure regulation is one of the most important negative feedback mechanisms in the body.

Parameter regulated is blood pressure Stimulus: is the change in blood pressure Receptor: Baroreceptor in carotid arteries and the aorta Sensory pathways: via visceral AFFERENT neurons Cardiovascular Control Center (CVCC): in brainstem performs integration Motor pathways: Parasympathetic and sympathetic Effectors: SA node, ventricular myocardium, and vascular smooth muscle - If arterial BP falls, increased sympathetic activity constricts beans, decreasing their holding capacity. - Vasoconstriction of the veins redistributes blood to the arterial side of the circulation and raises mean arterial pressure

Describe the function of precapillary sphincters in the intrinsic regulation of blood flow; these structures are sensitive to surrounding tissue factors and dilate to permit blood flow into capillary beds. Give examples of local factors that affect precapillary sphincters. NOTE: these are some of the same local factors that regulate arterioles.

Precapillary sphincter: - regulate intrinsic flow of blood. If relaxed: - blood flows through all capillaries in the bed. If constricted: - blood flow bypasses capillaries completely and blood flows through the metarterioles. EX of local factor waster products: - CO2, H, K, NO and O2.

Explain how the length of the refractory period prevents tetany in cardiac cells. (HINT: Think about skeletal muscle. The short action potential and long twitch creates a situation where skeletal tetany can occur. What happens to the action potentials in cardiac tissue that prevents tetany in cardiac tissue?)

Refractory period: the period of time after an action potential begins when an excitable cell temporarily loses its excitability. - Is long: lasts almost as long as entire muscle twitch (Lengthened by L-type calcium current) - Cannot be reexcited until its previous contraction is almost over. *For this reason, summation of contractions and tetany do not occur in cardiac muscle. *If cardiac muscle could undergo tetanus, the heart would not be able to function as a pump because it would not have a chance to relax and fill up with blood, a situation that would be lethal, arrthymia

Describe the series of events initiated by striking the patellar tendon with a percussion hammer that leads to extension of the lower leg (i.e. the knee jerk reflex)

Stimulus: - tap to tendon stretches muscle Receptor: - muscle spindle stretches and fires Afferent pathway: - Action potential travels through sensory neurons Integrating center: - sensory neuron synapses in spinal cord Efferent pathway 1: - Somatic motor neuron leads to effector of quadriceps muscle and response of quad contracting, swinging lower leg forward Efferent pathway 2: - Interneuron inhibiting somatic motor neuron leads to effector of hamstring muscle and response of hamstring stays relaxed, allowing extension of leg (reciprocal inhibition of antagonistic muscle)

Describe the venous contribution to venous return. How do the musculoskeletal pump, the respiratory pump, gravity, increases in preload and the venous valves contribute to venous return?

Venous return must match cardiac output EX: Increase in venous return will increase the preload Factors that promote return of the blood from veins to heart increase stroke volume (preload): 1. Musculoskelal pump: - skeletal muscle contractions (in the legs) compresses the veins and forces the blood towards the heart 2. Venous valves: ensure a one way flow of blood 3. Gravity: - pools blood toward the feet 4. Respiratory pump: - pressure changes with breathing that enhance blood flow 5. Sympathetic stimulation to the veins - Constriction and increases venous return 6. Increasing plasma volume - increases venous return (IV fluids, blood transfusion, aldosterone) -Increasing venous return affects the preload and cardiac output must match venous return so CO increases.

Compare/contrast the action potentials and properties of the typical ventricular cardiac myocyte vs. the SA nodal cells. Discuss membrane potential stability/instability at rest. Compare the voltage gated channel (Na+ , Ca2+ and K+ ) permeability to membrane potentials changes (depolarization, plateau and repolarization) during a typical cardiac myocyte AP and the SA node AP.

Ventricular myocyte · RMP of ventricular myocyte is much more negative (many K leak channels). · Depolarization due to voltage gated Na channels, plateau due to voltage-gated calcium channels, repolarization via voltage-gated K channels. SA nodal · Special gating of channels in nodal cell, open with repolarization which starts depolarization for next action potential - RMP is unstable, superthreshold depolarization due to L type voltage gated calcium channel, repolarization via voltage gated potassium

Describe the properties of the withdrawal reflex initiated by stepping on a sharp object.

Withdrawal reflex: flexion of a limb in order to withdraw the limb from a painful stimulus Process: 1. Pain stimuli: Stepping on a tack stimulates the dendrites (sensory receptor, nociceptor) of a pain-sensitive neuron 2. Primary sensory neuron generate action potential, propagates into spinal cord 3. Integrating center: in the spinal cord, sensory neuron activates interneurons that extend to several spinal cord segments 4. Interneurons activate motor neurons in several spinal cord segments · Result, the motor neurons generate action potentials propagate toward axon terminals 5. One collateral activates ascending pathways for sensation (pain) and postural adjustment (shift in center of gravity) 6. Acetylcholine released by the motor neurons causes the flexor muscles in the thigh (effectors) to contract, producing withdrawal of the leg (pulls foot away from painful stimulus) 7. Crossed extensor reflex supports body as weight shifts away from painful stimulus